Multicenter phase 2 trial of olaparib plus temozolomide for advanced uterine leiomyosarcoma

Uterine leiomyosarcoma (uLMS) is an aggressive subtype of soft-tissue sarcoma with frequent metastatic relapse after curative surgery. Chemotherapy provides limited benefit for advanced disease. Multiomic profiling studies have identified homologous recombination deficiency in uLMS. In preclinical studies where olaparib and temozolomide (TMZ) provided modest activity, the combination was highly effective for inhibiting uLMS tumor growth. NCI Protocol 10250 is a single-arm, open-label, multicenter phase 2 study evaluating the combination of olaparib and TMZ for advanced uLMS. The combination showed promising activity with an objective response rate of 27%, median progression-free survival 0f 6.9 months, and median duration of response 12.0 months. Thirty-one percent of patients had a genomic alteration in a homologous recombination repair gene, and 50% were homologous recombination-deficient by the RAD51 foci formation assay.